The trend of incidence and burden of neurological disease in Iran between 1990 and 2017: Based on global burden of disease estimations.

Neurological disease contributes significantly to morbidity and mortality in different ages and geographic areas around the world. The purpose of the current study was to investigate the incidence and disability-adjusted life years (DALYs) trend of neurological disease in Iran during 27 years ago. We used the data of the Global Burden of Disease (GBD) Study to estimate the incidence and DALYs of neurological disease in Iran in different age groups between 1990 and 2017. Age groups were defined in 5 groups including < 5 years, 5-14 years, 15-49 years, 50-69 years, and ≥ 70 years. The incidence number of neurological disease during 1990 to 2017 increased from 7.5 million to more than 12 million and the incidence rate grew as much as 1400 per 100000 populations in Iran. Totally, headache, epilepsy, and Alzheimer were the most common neurological diseases according to incidence and had the most values of DALY in Iran. The highest incidence and DALY of neurological disease was observed in the age group of 15-49 years. This study showed that the incidence and burden of neurological diseases had a dramatic increasing trend during 27 years ago in Iran. Consequently, it is necessary to investigate the causes of the growing trend in future studies.

Increased life span and decreased fertility have caused a demographical transmission from mainly young populations to older and ageing ones, causing increases in the cognitive disorders such as Alzheimer disease (AD) and other dementias and Parkinson's disease (PD). 6 In addition, neurological disorders cause a lot of costs to patients and the treatment system in the countries. A research accomplished in Europe during 2004 calculated that the yearly expenditure of neurological disorders [such as dementia, epilepsy, migraine and other headaches, multiple sclerosis (MS), PD, and stroke] reached €139 billion (nearly US$180 billion). The mentioned research only counted direct non-medical expenditures (e.g., society surveillance and informal care) and dismissed indirect charges and intangible expenditures. 7 Currently, it is estimated that neurological diseases and their squeals affect as many as a billion individuals in the world. They affect hundreds of millions of people in the world: more than 50 million people have epilepsy and about 47 million people are affected by dementia globally -AD is the most common cause of dementia and may contribute to 60%-70% of cases. The prevalence of migraine is more than 10% worldwide. 8,9 Since the neurological diseases often produce long-dated disability and most of them occur at an early age, prevalence and mortality indices underestimate their disability in the population. Therefore, it is necessary to be a combined measure of survival and health status among survivors to create a single measure. 9,10 To determine the burden of disease, the 1990 Global Burden of Disease (GBD) Study introduced a time-based measure that considers both premature mortality [years of life lost (YLL) due to premature mortality] and disability [years of healthy life lost due to disability (YLD)]. The summation of these two parts provides disabilityadjusted life years (DALYs) -an indicator of the latter path of healthy life (years expected to live in full health status) lost due to the occurrence of specific diseases and injuries. One DALY can be considered as one of the lost healthy life years and the burden of disease as an index of the difference between present health status and ideal health condition in which anyone lives in old age without disease and disability. 11 Epidemiological study plays a main role in the identification of disease occurrence and patterns as well as related risk factors and etiology. 12 The purpose of the current study was to investigate the incidence and DALY trend of neurological disorders in Iran during the years of 1990 and 2017.

Materials and Methods
Study type: Using data from the GBD study of 1990 to 2017, this study presented the trend of incidence and DALYs of neurological disorders in Iran by age groups. The 2017 GBD study was a comprehensive and systematic effort to calculate the global and regional comparative risk assessment of morbidity, mortality, and DALYs caused by different risk factors and diseases according to data-gathering and estimations of 354 types of diseases and injuries and 282 causes of death in 195 countries. 13 Data source: The process for non-fatal evaluation begins with the incorporation of data sources from several possible origins which include 21 possible Global Health Data Exchange (GHDx) data types ranging from scientific literature to epidemiological surveillance data. GBD collaborators network provided 2842 data sources for GBD 2017. They analyzed 21100 sources of epidemiological surveillance data (country-years of disease reporting) for GBD 2017 and 4734 sources of disease registry data. For non-fatal estimation, they did systematic data and literature searches for 82 nonfatal causes and one impairment, which were updated in February 11, 2017. 13 Calculations were performed for age groups of < 5, 5-14, 15-49, 50-69, ≥ 70 years as well as all age groups. AD, PD, epilepsy, MS, motor neuron diseases (MNDs), other neurological disorders, and all neurological diseases were included in the study. Firstly, through a comprehensive systematic review of published and unpublished data, a Bayesian meta-regression method was performed to ensure consistency between incidence rate and cause of death for each condition. 14 In this study, each measure of incidence and DALY were presented in three ways: number, rate, and percentage. The associated number of each event in each age group was divided into the population in groups and expressed in 100000 populations for the rate calculation. In addition, the number of related cases in each age group was divided into the total number of that event and multiplied in 100 for estimation of proportion. All calculations and statistical analysis were performed by GBD Results Tool software.

Incidence of neurological disorders
Numbers: According to GBD, the number of total neurological disorders new cases in all age groups, during the years of 1990 and 2017, significantly increased from about 7.5 million to more than 1200 million. During the same period, the incidence numbers of each neurological disease increased in all age groups and most of the growth was related to headaches, AD, and epilepsy, respectively. Also, based on the relationship of incidence cases of neurological disorders with age, except for epilepsy and MNDs, the number of other diseases was ascending and raised with age and the most number of all neurological disorders were seen in the age group of 15-49 years ( Table 1, A).
Rates: According to GBD, during the years of 1990 and 2017, the incidence rate of all neurological disorders increased as much as 1400 per 100000 populations in all age groups. According to the type of disorders, the highest values were related to headaches, epilepsy, and AD, respectively, both in 1990 and 2017; but AD surpassed epilepsy in 2017. Moreover, in terms of the relationship of neurological disorders with age, epilepsy mostly occurred in age group of 5-14 years; headache, MNDs, and MS were more prevalent in 15-49 years age group, and the rest disorders were more seen in the age group of 70 and more years old (Table 1, B).
Proportion: According to GBD, both in 1990 and in 2017, from 100% incidence cases of neurological diseases, more than 99% were due to headaches followed by AD and epilepsy, respectively. Moreover, by comparing 1990 and 2017, except for headaches, the incidence proportion of most diseases increased in any age group; the most increases were seen for AD (0.27%), epilepsy (0.06%), and PD (0.04%). In addition, more than 55% of all neurological disorders firstly occurred in the age group of 15-49 years in 1990; also, this age group had the highest proportion (66% of all neurological disorders incidence) in 2017 (Table 1, C).

DALYs of neurological disorders
Numbers: According to GBD, during years of 1990 and 2017, the number of all neurological disorders DALY nearly doubled in all age groups. In addition, the DALY number of most disorders increased during these years in all age groups and the highest values corresponded to headaches, AD, and PD, respectively; in contrast, the epilepsy burden decreased during these years. It is interesting to note that both in 1990 and 2017, more than two thirds of burden of all neurological disorders were seen in the age group of 15-49 years ( Table 2, A).
Rates: According to GBD, although the burden of all neurologic disorders increased during 1990 to 2017 in all age groups, its value was halved in the first age group and slightly decreased in the second age group. It appears that except for epilepsy, the DALY rate of other diseases increased during these years in all age groups and the most growth was related to headaches, AD, and PD, respectively (Table 2, B).
Proportion: According to GBD, headaches, epilepsy, and AD had the most significant role in the burden of diseases during years of 1990 and 2017. In 2017 compared with 1990, the DALY percentage of AD, PD, and MS increased in all age groups, but the corresponding values of epilepsy and headache declined. The highest DALY of all neurological disorders occurred in the group of 15-49 years both in 1990 and 2017, but the age distribution of each disease was different from other ones ( Table 2, C).
In figure 1, all ages incidence (part A) and DALY (part B) trend of most important neurological disorders such as AD and PD were presented without considering age structure changes of population since 1990 to 2017. Approximately, the movement direction of the incidence and burden of all diseases is similar. Interestingly, during this time, the incidence and burden of AD increased significantly; in contrast, epilepsy figures had a good downward trend; but there was no significant change in the statistics of other neurological diseases. Figure 2 shows the age-adjusted incidence (A) and DALY (B) trend of aforementioned neurological disorders from 1990 to 2017. By comparing it with figure 1, although it can be seen that AD incidence and burden and so epilepsy are still much higher than the rest of the disorders, their trend did not change significantly over time. On the contrary, the incidence of epilepsy increased during this time, and AD burden declined from 1990 to 2000.

Discussion
The present study is a representative and population-based epidemiological study that was conducted on neurological disorders using GBD data in Iran.    Epidemiological studies identify the risk factors and pattern of disease. According to the current study, both in 1990 and 2017, headaches, epilepsy, and AD were the most common neurological diseases, respectively. During these years, incidence and DALY of total neurological disorders impressively increased in all age groups. The highest incidence and DALY numbers and percentages of all neurological disorders were seen in the 15-49-year group. Growth in both animal and human models is associated with changes in the performance of central cholinergic neurons. These alterations mainly involve reducing the level of cholinergic receptors, decreasing the synthesis and release of acetylcholine, and a significant reduction in the number of muscarinic cholinergic neurons that may be related to age-related memory impairment such as AD. 30,31 Nevertheless, it is recommended that in the future more studies examine the role of other factors in increasing the incidence and burden of neurological disorders. Although GBD uses various data sources from scientific literature to epidemiological surveillance information for information collection and estimation, according to the Iranian neurologists opinion, the GBD values of some neurological disorders, in particular, for MS are very different and lower than the reality and their observed trend in the last 27 years. As a result, the need to set up neurological disorders registry system in Iran is felt more than ever before, because it could help policy makers in accurate estimation and predicting or preparing facilities in the future.

Conclusion
The results of the current study showed that the incidence and burden of neurological disorders had a dramatic upsurge trend during the years 1990 and 2017 in Iran. Consequently, it is necessary to investigate the causes of this increase in future studies.